Current working hypotheses state that tardive dyskinesia results from a relative dopaminergic hyperfunction and/or an acetylcholinergic relative hypofunctioning. While there is ample data to support the bases of these hypotheses, we have not been able to explain uniformly all the clinical findings associated with tardive dyskinesia, nor has there been a uniform treatment developed for this syndrome. With the clarification in the past few years of the striatal-nigral feedback system that is predominantly GABA-mediated, it is evident that any complete explanation of tardive dyskinesia as a disease state representing the disruption of normal basal ganglia function must include a thorough understanding of the GABA role in maintaining normal movement. It is the intent to enhance brain GABA by inhibiting the degradative enzyme GABA transaminase in both humans and animals. The human investigation will utilize a double-blind non-crossover paradigm to study DPA over a wide dose range during a 4-week period. Clinical changes will be monitored by an objective physiological tremorgraph and by two rating scales, and will be correlated with DPA blood levels. The animal studies will investigate the acute and chronic effects of DPA on spontaneous behavior on the hyperdopaminergic-induced behavioral stereotypies and on an animal model of tardive dyskinesia that produces presumed dopamine receptor hypersensitivity following chronic neuroleptic drugs. Brain basal ganglia tissue assays of GABA, GABA-T, SSA-DH and GHB will be measured. Additionally, dopamine and GABA receptors will be quantified and the data combined with the tissue assay results and compared with the behavioral findings.